The concept of "interference" has played a central role in theories of perception and memory. For over 100 years, psychological experimentation and theory have been focused on understanding how interference is resolved in perceptual, memory, and motor processes. In current parlance, the resolution of interference requires the engagement of executive processes to control the trajectory of cognition. We propose research on interference-resolution that has two main goals: One is to understand mechanisms of interference- resolution operating at different states of processing, leading to creation of psychological and neural models of these mechanisms. The second goal is to apply this basic research to Major Depressive Disorder (MOD). For a time, the predominant view of interference-resolution rested on the assumption that there is a single mechanism to control interference. This mechanism was claimed to be inhibition of irrelevant or distracting information. However, other research has led to the view that there are multiple mechanisms that may vary from one task to another. We ask how these mechanisms are similar to and different from one another. Studying individuals diagnosed with major depression provides an important model for testing our assumptions about the neurological and cognitive environment associated with these processes. This is because the cortical areas that are active during interference-resolution overlap those that have been implicated in depression. Further, understanding the cognitive processes that are dysfunctional in depressives will further help to refine cognitive models of depression, leading to more efficacious therapy. We propose to use variations of the item-recognition task to investigate issues of interference-resolution. Modifying this paradigm permits us to study interference that occurs at the time of encoding, when information is stored in working memory, and at the time of response selection. There is some indication that patients with clinical depression have compromised abilities to resolve interference at all of these stages, but interference in working memory appears to be particularly prominent. We hypothesize that a deficit in removing unwanted information from working memory is related to rumination in depressed patients, and that interference-resolution deficits at other states of processing may be related to other aspects of the disease. Relevance of this research to public health: Patients with Major Depressive Disorder often engage in what is called rumination, continued focusing on negative thoughts that recycle over and over again. The proposed research examines the cognitive and brain deficits that may lead to rumination in the hope that these may be singled out for treatment.